- Design
- Phase 2, randomised, double-blind, placebo-controlled, dose-ranging
- Population
- 493 adults with obesity (mean BMI 36.7), without diabetes, in Poland, Romania and the USA
- Primary outcome
- Percentage change in body weight at 28 weeks
- Effect
- Placebo-adjusted −6.2% (1 mg) to −8.1% (5 mg; 95% CI −9.7 to −6.5)
ZUPREME 1, in The Lancet Diabetes & Endocrinology (29 September), randomised 493 adults with obesity and without diabetes, 5:1, to one of five weekly petrelintide doses or placebo. Mean baseline weight was 107 kg.
At 28 weeks, weight fell 7.9% to 9.8% across doses against 1.7% on placebo — placebo-adjusted differences of 6.2% to 8.1%. Weight kept falling to 42 weeks, up to 10.7%. Nausea affected 20% on petrelintide and 6% on placebo, mostly mild and during escalation; vomiting and diarrhoea were no more common than placebo.
Amylin works through satiety rather than the incretin pathway, so interest centres on tolerability and on combination with GLP-1-based drugs. These numbers are below what current incretin drugs achieve over a similar time. This is phase 2, industry funded and mostly in White participants; it is not available outside trials.
- Placebo-adjusted weight loss was about 6–8% at 28 weeks, with no clear gain above 5 mg
- Nausea affected one in five, with little vomiting or diarrhoea
- Participants had no diabetes; glycaemic effects in type 2 diabetes are not yet known
- Not licensed anywhere; patients asking can be told it remains in trials
Why it matters
A non-incretin route to weight loss with fewer gastrointestinal effects would widen options for people who cannot tolerate GLP-1 drugs.
Don't overread it
Phase 2 with a 28-week primary endpoint — durability, cardiovascular outcomes and effects in diabetes are untested.
The statistics, in plain English
Doses from 5 mg to 9 mg gave overlapping confidence intervals (around −8%), so higher doses did not clearly add weight loss. The 5:1 randomisation means the placebo group was small, about 80 people, which widens the uncertainty around each comparison.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for diabetes & endocrinology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free